Genotyping of Clinical Parameters in Age-Related Macular Degeneration

Battu, Priya; Sharma, Kaushal; Thangavel, Rajarathna; Singh, Ramandeep; Sharma, Suresh; Srivastava, Vinod K.; Anand, Akshay

doi:10.2147/opth.s318098

Cited by 1 publication

(1 citation statement)

References 50 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the highest proportion, the autosomal recessive RP (ARRP) has remarkably heterogeneous genotypes (bottom row of Figure 1B ), which are known to, along with other factors (e.g., environment, gender, and epigenetics), result in the different levels/patterns of retinal degeneration in each individual ( Chang et al, 2011 ). Similar with RP, AMD genotypes are also variegated, which include single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor ( VEGF ), and pigment epithelium-derived factor ( PEDF ), complement factor H ( CFH ), and high-temperature requirement factor A1 ( HTRA1 ) genes ( Mori et al, 2010 ; Black and Clark, 2016 ; Battu et al, 2022 ). Each genotype disrupts distinct pathways and/or functions of the retina and expresses unique phenotypes ( Berger et al, 2010 ; Verbakel et al, 2018 ), raising a possibility that electrically-evoked spiking responses (hereafter referred to as electric responses) of RGCs are significantly different depending on the genotype.…”

Section: Introductionmentioning

confidence: 99%

Electrically-evoked responses for retinal prostheses are differentially altered depending on ganglion cell types in outer retinal neurodegeneration caused by Crb1 gene mutation

Roh

Otgondemberel

Eom

et al. 2023

Front. Cell. Neurosci.

View full text Add to dashboard Cite

BackgroundMicroelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation.MethodsWe first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials.ResultsIn the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = −0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models.ConclusionOur results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research.

show abstract